Obstructive coronary diseases may be caused by a stable or an unstable plaque. An unstable atherosclerotic plaque is vulnerable to rupture and to subsequent thrombogenic reaction, which can lead to sudden death. In general, when the associated stenosis of a stable plaque reaches a certain threshold, it may cause a lack of myocardium perfusion and associated chest pain or angina pectoris.
Historically, the first endovascular mechanical treatment was introduced in 1977 by Andreas Gruentzig who introduced the angioplasty balloon. Percutaneous angioplasty was however associated with a phenomenon called restenosis. Restenosis is essentially the re-obstruction of the vessel caused by vessel recoil, remodeling and hyperplasia. In order to treat the acute recoil and limit the restenosis process, Palmaz-Schatz introduced a new medical implant, the stent, in 1986. A new phenomenon was then observed, in-stent restenosis, or the re-obstruction inside the stent. However, the restenosis rates associated with balloon angioplasty (40-60%) were greatly improved with the advent of stents in 1986 (20-30%) which nevertheless still constitutes a relatively high rate. In order to treat the in-stent restenosis process, Drug Eluting Stents (DES) were introduced. DES were initially coated with antiproliferative and anti-thrombotic compounds. The first DES (Cypher, Cordis) was approved in Europe in 2002. DES initially were effective in limiting restenosis with reported rates between 0 and 16%. However, a few years following their introduction, a serious phenomenon was reported. Late thrombosis (reported by Camenzin on the “Black Sunday” in 2006) was demonstrated to be associated with DES. It was subsequently shown that the rate of late thrombosis continues to increase with time following the implantation. This is phenomenon is of great concern since thrombosis is a life threatening event possibly leading to myocardium infarction.
The causes of late thrombosis are not fully elucidated but processes like chemical compound effect, chronic inflammation and vessel wall injury are reported in the literature. Concerning chronic inflammation and vessel wall injury, a direct link was demonstrated between stent fracture and In-Stent Restenosis (ISR) and thrombosis. ISR is observed both with bare metal stents (BMS) and DES with respective rates of 20-25% and 0-16.7%. The relation with DES fracture was shown to be more frequent than previously thought. The reason is that most of the time stent fracture is clinically silent. However, with imaging modalities, the reported incidence is 1-2% and pathologic investigations reported an incidence of 29% with about 5% associated with adverse effects: inflammation, ulceration, avulsion, ISR, thrombosis.
Furthermore, it was also shown that stent fractures are correlated with anatomical location (tortuosity), with stent fractures more common in the Right Coronary Artery (RCA) with a rate of 57% than in the Left Anterior Descending (LAD) with a rate of 34%, and stent design and lesion types. In addition, stress fractures are also strongly correlated with time: stents may get fully broken over long periods of time. For example, a few broken struts have been reported after implantation times of about 172 d and full stent fracture after implantation times of 1800 d.
This problem is inherently a mechanical problem linked to the notion of fatigue of material. Every material subjected to cyclic loading, such as heart beats, will fatigue and eventually fail. Possible solutions for stent design include developing a superior material for manufacturing the stent for higher longevity and biodegradable stents. Indeed, a biodegradable stent would essentially disappear once it has performed its temporary scaffolding task and thus avoid being subjected to cyclic fatigue.
It is with this perspective that the Igaki-Tamai stent, the first polymeric biodegradable stent made of poly-L-lactide polymer, was introduced in 2003. Since polymers have mechanical properties that are about 2 orders of magnitude lower than metals, mechanical integrity problems were reported, including acute recoil. Given their relative weaker mechanical properties, larger struts are required to ensure proper scaffolding of the vascular wall. The thicker struts, in turn, may cause more resistance to blood flow and may be too large to implant in many blood vessels. Their capacity to properly scaffold plaques with calcification was also mentioned. In addition, larger struts were also associated with more vessel injuries, thus potentially leading to more vessel response and hyperplasia.
At about the same time, biodegradable metallic stents were investigated. The principle was to exploit the property of reactive metals to corrode for biodegradation. The initial selected metal was magnesium. The concept of biodegradation has been shown to work. However, there are several limitations associated with the use of magnesium (WE magnesium). Similar to polymers, magnesium has mechanical properties that are much lower than the current super alloys used for commercial stents (such as 316L stainless steel, L605 cobalt-chromium alloy). As a consequence, thicker struts are also required, and these are associated with the same problems of possible flow disturbances and wall injury. Indeed, negative remodelling was recently demonstrated with the use of the magnesium-based stent.
More recently, other reactive metal alloys were investigated, including iron-manganese alloys and electroformed iron. These alloys have relatively better mechanical strength than magnesium-based alloys. However, the iron-manganese alloys have quite large metallic grains (100 microns), which is an issue given that a stent strut dimension is below 100 microns. Electroformed irons have much smaller grain sizes (2-8 microns) but have limited ductility. Furthermore, control of the degradation rate of these alloys is a challenging task.
Some stents, such as the stent proposed in U.S. Pat. No. 8,080,055 by Atanasoska et al. and issued Dec. 20, 2011, use galvanic corrosion between a core of a stent and a coating made of a different material to promote degradation of the stent in situ. However, such stents require thick struts having a layered structure. This structure also results in heterogeneous degradation as the cathodic layers will remain uncorroded and the anodic layer will also degrade non-homogeneously.
Accordingly, there is a need in the industry to provide an improved bioresorbable stent and other bioresorbable medical devices, along with methods of manufacturing such medical devices. An object of the present invention is therefore to provide such devices and methods.